The present invention relates to novel prostaglandins and prostacyclins, a process for their preparation and their use as medicinal agents.
As biological conversion products of triply-, quadruply- (arachidonic acid), and quintuply-unsaturated, naturally occurring C.sub.20 -fatty acids, great therapeutic significance is attributed, above all, to prostaglandins, prostacyclins, and thromboxanes, especially in the form of their analogs.
The functionality of their 1-carboxy group is of great importance for the interaction of these compounds with receptors, i.e., with respect to selectivity and duration of biological efficacy, as well as for metabolism (.beta.-oxidation). Compared with the 1-carboxylic acids, the 1-esters, 1-amides, and, especially, 1-sulfonamides or 1-acylamides show a different spectrum of biological activity [see, inter alia, T. K. Schaaf and H. J. Hess, J. Med. Chem. 22: 1340 (1979)].
However, all of these groups are either neutral, such as the 1-esters or 1-amides, or they are acidic, such as the 1-acylsulfonamides. Thus, there has been great interest in converting the 1-carboxy group in prostaglandins, prostacyclins, and thromboxanes, as well as the analogs thereof, into alkaline derivatives without changing their valence.
It is now readily possible, with the aid of a new method described in PCT/DE81/00225, filed Dec. 14, 1981, whose disclosures are incorporated by reference herein, to convert the 1-carboxy group of prostaglandins and prostacyclins, as well as the derivatives thereof, into the corresponding basic .DELTA..sup.2 -oxazolines, .DELTA..sup.2 -thiazolines and .DELTA..sup.2 -imidazolines, respectively, as well as into their higher-membered analogs, such as, for example, 5,6-dihydro-4H-1,3-oxazines, 5,6-dihydro-4H-1,3-thiazines, and tetrahydropyrimidines.
These novel derivatives have a different and more selective spectrum of biological efficacy and, especially in the case of the prostacyclins, are chemically and metabolically considerably more stable and thus of longer duration of efficacy than prostacyclin (PGI.sub.2).